Synthesis of lipid A derivatives and their interactions with polymyxin B and polymyxin B nonapeptide
| Autor: | Sannali Matheson, Ning Yin, Paul B. Savage, Ryan L. Marshall |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
medicine.drug_class
Stereochemistry Antibiotics Peptide Buffers Calorimetry Biochemistry Catalysis Lipid A Colloid and Surface Chemistry Anti-Infective Agents 2-Naphthylamine medicine Molecule Solubility Fluorescent Dyes Polymyxin B chemistry.chemical_classification Cationic polymerization Titrimetry General Chemistry Anti-Bacterial Agents chemistry lipids (amino acids peptides and proteins) Titration medicine.drug |
| Zdroj: | Journal of the American Chemical Society. 125(9) |
| ISSN: | 0002-7863 |
| Popis: | Lipid A is the causative agent of Gram-negative sepsis, a leading cause of mortality among hospitalized patients. Compounds that bind lipid A can limit its detrimental effects. Polymyxin B, a cationic peptide antibiotic, is one of the simplest molecules capable of selectively binding lipid A and may serve as a model for further development of lipid A binding agents. However, association of polymyxin B with lipid A is not fully understood, primarily due to the low solubility of lipid A in water and inhomogeneity of lipid A preparations. To better understand lipid A-polymyxin B interaction, pure lipid A derivatives were prepared with incrementally varied lipid chain lengths. These compounds proved to be more soluble in water than lipid A, with higher aggregation concentrations. Isothermal titration calorimetric studies of these lipid A derivatives with polymyxin B and polymyxin B nonapeptide indicate that binding stoichiometries (peptide to lipid A derivative) are less than 1 and that affinities of these binding partners correlate with the aggregation states of the lipid A derivatives. These studies also suggest that cooperative ionic interactions dominate association of polymyxin B and polymyxin B nonapeptide with lipid A. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|